The impact of antigen density and antibody affinity on antibody-dependent cellular cytotoxicity: relevance for immunotherapy of carcinomas

We studied the sensitivity of human melanoma (Bro strain) xenografts to drugs of the nitrosoalkylurea (NAU) class: nitrosomethylurea (NMM), karmustin (BCNU), nimustin (ACNU), nitrulin, and ADEKO. High antitumor activity of NAM was shown when the drugs were applied not only at the early, but also at the late stages of tumor progression (tumor mass 400 and 1200 mg, respectively). The therapeutic effect of the drugs was estimated with the use of criteria characterizing the kinetics of tumor regression, increased life span, and survival of treated animals. After early administration of the drugs (Day 4 after tumor transplantation), 67% and 50% of animals survive under the influence of nitrulin and ACNU, respectively, while the rate of tumor regression increased in the sequence nitrulin < karmustin < NMM < ACNU. After late administration (11 days after tumor transplantation), NMM was most effective at increasing survival (35% of survived animals by 35 days of observation), while the rate of tumor regression increased in the sequence ADEKO < NMM < karmustin < nitrulin < ACNU.     

Dacryocystitis associated with nasolacrimal duct cyst

An infant presented with persistent epiphora after successful probing of the lacrimal system. Examination of the nose showed a cystic structure occluding lower portion of the lacrimal drainage system. In cases of recurrent obstruction, nasal examination and endoscopic marsupialization may help guide the clinician towards the most appropriate treatment.     

Reply to Professors Purchase and Gelbke

BACKGROUND AND OBJECTIVES: Laparoscopic pyelolithotomy was performed in a pelvic kidney with a large renal pelvis calculus. METHODS AND RESULTS: Laparoscopic pyelolithotomy was successfully performed in a pelvic kidney with an operative time of 310 minutes. The use of intraoperative fluoroscopy and a semi-automatic suturing device greatly facilitated the procedure. The patient's operative pain was managed with 3 doses of ketorolac; she resumed a regular diet the day after surgery, and was discharged on the first postoperative day. CONCLUSIONS: For patients with a large stone in the renal pelvis of an ectopic kidney, laparoscopic pyelolithotomy provides an effective approach.     

Channels formed by the transmembrane helix of phospholamban: a simulation study

Phospholamban is a small membrane protein which can form cation selective ion channels in lipid bilayers. Each subunit contains a single, largely hydrophobic transmembrane helix. The helices are thought to assemble as a pentameric and approximately parallel bundle surrounding a central pore. A model of this assembly (PDB code IPSL) has been used as the starting point for molecular dynamics (MD) simulations of a system consisting of the pentameric helix bundle, plus 217 water molecules located within and at either mouth of the pore. Interhelix distance restraints were employed to maintain the integrity of the helix bundle during a 500 ps MD simulation. Water molecules within the pore exhibited reduced diffusional and rotational mobility. Interactions between the alpha-helix dipoles and the water dipoles, the latter aligned anti-parallel to the former, contribute to the stability of the system. Analysis of the potential energy of interaction of a K+ ion as it was moved through the pore suggested that unfavourable interactions of the cation with the aligned helix dipoles at the N-terminal mouth were overcome by favourable ion-water interactions. Comparable analysis for a Cl ion revealed that the ion-(pore + water) interactions were unfavourable along the whole of the pore, increasingly so from the N- to the C-terminal mouth. Overall, the interaction energy profiles were consistent with a pore selective for cations over anions. Pore radius profiles were used to predict a channel conductance of 50 to 70 ps in 0.2 M KCl, which compares well with an experimental value of 100 ps.     

Intraventricular galanin modulates a 5-HT1A receptor-mediated behavioural response in the rat

The present studies have examined whether the neuropeptide galanin can modulate brain serotoninergic (5-HT) neurotransmission in vivo and, particularly, 5-HT1A receptor-mediated transmission. For that purpose, we studied the ability of galanin (given bilaterally into the lateral ventricle, i.c.v.) to modify the impairment of passive avoidance retention induced by the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propyloamino)tetralin (8-OH-DPAT) when injected prior to training. This impairment appears to be mainly related to activation of 5-HT1A receptors in the CNS. Galanin dose-dependently (significant at 3.0 nmol/rat) attenuated the passive avoidance impairment (examined 24 h after training) induced by the 0.2 mg/kg dose of 8-OH-DPAT. This 8-OH-DPAT dose produced signs of the 5-HT syndrome indicating a postsynaptic 5-HT1A receptor activation. Furthermore, both the impairment of passive avoidance and the 5-HT syndrome were completely blocked by the 5-HT1A receptor antagonist WAY 100635 (0.1 mg/kg). Galanin (0.3 or 3.0 nmol) or WAY 100635 (0.1 mg/kg) failed by themselves to affect passive avoidance retention. 8-OH-DPAT given at a low dose 0.03 mg/kg, which presumably stimulates somatodendritic 5-HT1A autoreceptors in vivo, did not alter passive avoidance retention or induce any visually detectable signs of the 5-HT syndrome. Galanin (0.3 or 3.0 nmol) given i.c.v. in combination with the 0.03 mg/kg dose of 8-OH-DPAT, did not modify passive avoidance. The immunohistochemical study of the distribution of i.c.v. administered galanin (10 min after infusion) showed a strong diffuse labelling in the periventricular zone (100-200 microm) of the lateral ventricle. Furthermore, in the dorsal and ventral hippocampus galanin-immunoreactive nerve cells appeared both in the dentate gyrus and the CA1, CA2 and CA3 layers of the hippocampus. In the septum only endogenous fibres could be seen while in the caudal amygdala also galanin-immunoreactive nerve cells were visualized far away from the labelled periventricular zone. At the level of the dorsal raphe nucleus a thin periventricular zone of galanin immunoreactivity was seen but no labelling of cells. These results suggest that galanin can modulate postsynaptic 5-HT1A receptor transmission in vivo in discrete cell populations in forebrain regions such as the dorsal and ventral hippocampus and parts of the amygdala. The indication that galanin administered intracerebroventrically may be taken up in certain populations of nerve terminals in the periventricular zone for retrograde transport suggests that this peptide may also affect intracellular events.     

STD/HIV prevention in Turkey: planning a sequence of interventions

This study was initiated to assess which mix of early STD/HIV prevention interventions would potentially be effective, cost-effective and sustainable in Turkey; and to program an intervention sequence to maximize synergy among the interventions. During rapid assessment we: 1) reviewed past issues of 3 leading newspapers; 2) collected information on TV coverage; 3) interviewed key informants including taxicab drivers, hotel employees, grocery store owners, academicians in public health and law, investigators of STD/HIV and reproductive tract infections, and officials in the ministry of health; 4) reviewed available evidence on STD/HIV morbidity, sexual behavior patterns, migration patterns and same/opposite gender sex trade. We found: 1) discrepancies between decision makers' perceptions and social realities with respect to the epidemiology of sexual behavior and STDs, and the state of public health programs; 2) discrepancies between sexual practices and public expression regarding sexual practices; 3) economic, demographic, and political pressures in Turkey and in surrounding countries for the expansion of prostitution; 4) a sexual double standard and gender specific migration patterns which sustain a high demand for commercial sex; 5) patterns of health care seeking behaviors and provision of STD clinical services which indicate other STDs may play a very important role in spread of HIV infection; 6) an important mass media role in opinion formation; 7) consensual denial of risk for the majority based on beliefs embedded in machismo, nationalism and religion, and a resulting marginalization and externalization of STD/HIV risk; 8) high prevalence of syphilis among both Turkish and immigrant female prostitutes in Istanbul (early latent 8 and 13%; late latent 0 and 4%; previous history 9 and 22%) 9) and high rates of syphilis among male prostitutes (early latent 11%, late latent 21% and previous history 58%). We concluded that interventions should initially include, in the following order; 1) awareness raising for decision makers and opinion leaders including members of parliament and mass media; 2) awareness raising for members of the general population; 3) needs assessment and intervention development for sex workers; 4) training in HIV and other STDs for medical personnel; and 5) quality assurance and control for laboratory procedures for STDs/HIV.     

Extensive epidural hemangioma with skin and bone involvement. A case report

STUDY DESIGN: This is a case report. OBJECTIVE: To report and to examine the clinical findings and management of epidural cavernous hemangioma. SUMMARY OF BACKGROUND DATA: Spinal epidural cavernous hemangiomatous malformation is a very rare entity. Only 20 cases of this disease have been reported in the literature. METHODS: The case of a 20-year-old woman with spinal epidural cavernous hemangioma was reviewed. RESULTS: The clinical presentation, diagnosis, and therapy of this disease are discussed. CONCLUSION: The treatment of epidural hemangioma consists of total or subtotal excision of the lesion, depending on the relation of the lesion to the spinal cord.     

Inhibition of the microsomal triglyceride transfer protein blocks the first step of apolipoprotein B lipoprotein assembly but not the addition of bulk core lipids in the second step

The microsomal triglyceride transfer protein (MTP) is required for assembly and secretion of the lipoproteins containing apolipoprotein B (apoB): very low density lipoproteins and chylomicrons. Evidence indicates that the subclasses of these lipoproteins that contain apoB-48 are assembled in a distinct two-step process; first a relatively lipid-poor primordial lipoprotein precursor is produced, and then bulk neutral lipids are added to form the core of these spherical particles. To determine if either step is mediated by MTP, a series of clonal cell lines stably expressing apoB-53 and MTP was established in non-lipoprotein-producing HeLa cells. MTP activity in these cells was approximately 30%, and apoB secretion was 7-33% of that in HepG2 cells on a molar basis. Despite having robust levels of triglyceride and phospholipid synthesis, these cell lines, as exemplified by HLMB53-59, secreted >90% of the apoB-53 on relatively lipid-poor particles in the density range of 1.063-1.21 g/ml. These results suggested that coexpression of MTP and apoB only reconstituted the first but not the second step in lipoprotein assembly. To extend this observation, additional studies were carried out in McArdle RH-7777 rat hepatoma cells, in which the second step of apoB-48 lipoprotein assembly is well defined. Treatment of these cells with the MTP photoaffinity inhibitor BMS-192951 before pulse labeling with [35S]methionine/cysteine led to an 85% block of both apoB-48 and apoB-100 but not apoAI secretion, demonstrating inhibition of the first step of lipoprotein assembly. After a 30-min [35S]methioneine/cysteine pulse labeling and 120 min of chase, all of the nascent apoB-48 was observed to have a density of high density lipoproteins (1.063-1.21 g/ml), indicating that only the first step of lipoprotein assembly had occurred. The addition of oleic acid to the cell culture media activated the second step as evidenced by the conversion of the apoB-48 high density lipoproteins to very low density lipoproteins (d < 1.006 g/ml) during an extended chase period. Inactivation of MTP after completion of the first step, but before stimulation of the second step by the addition of oleic acid, did not block this conversion. Thus, inhibition of MTP did not hinder the addition of bulk core lipid to the primordial lipoprotein precursor particles, indicating that MTP is not required for the second step of apoB-48 lipoprotein assembly.     

Infant weaning practises of some Idoma women in Makurdi, Nigeria

The weaning practices in infants aged 4-9 months of two hundred Idoma women resident in Makurdi were examined. A pre-tested standard questionnaire was used to collect data from mothers who regularly visited the post-natal health clinics in Makurdi. The results showed that better educated mothers breast fed for a shorter time or planned to cease breast feeding after a shorter period than mothers who had little education or no formal training. Most mothers (97%) fed milk formula which they claimed was used to supplement breast milk and was good for their babies. The most influential factors were the hospital and the husband. The majority of the mothers fed pap; 73% using corn in its preparation, with 91% of them storing such paps in flask. More than half of the mothers used a bottle in feeding the paper or gruel to their infants while a similar proportion (65.5%) fed legumes to their infants in addition to fruits. The implications of these practices in comparison with other ethnic groups is discussed.